ABSTRACT
The Chief Medical Officer for England, Professor Sally Davies, and colleagues argue that it is time for a ‘fifth wave’ of public health, and influential organisations are seeking to advance this agenda. The fifth wave would progress from earlier shifts in public health, through... Read more

ABSTRACT
The Chief Medical Officer for England, Professor Sally Davies, and colleagues argue that it is time for a ‘fifth wave’ of public health, and influential organisations are seeking to advance this agenda. The fifth wave would progress from earlier shifts in public health, through structural, biomedical, clinical, and, most recently, social waves, towards a wave wherein the public’s health is recognised as a common good to be actively promoted through participation of the public as a whole. Davies and colleagues categorise this fifth wave as cultural, emphasising the cultivation through institutional, social, and physical environments of shared beliefs, values, and behaviours in which pro-health attitudes—individually and at a societal level—are normalised. They advocate for their agenda within a political context that has undermined the highest attainable standards of health through an individualism that defies what is shown by epidemiological studies on the social determinants of health. Focusing on the practical case study of the ‘tobacco endgame’, my paper examines the fifth wave agenda through a public health ethics and law perspective. It critically explores the viability of political justifications for a public health policy strategy that works through a long-game, cross-sector approach of progressive achievement of change. This requires a study both of the justification of the goal that is aimed at and, crucially, the means of achieving it. Given the dominant political context, it is unsurprising that efforts are made to find ‘neutral’ normative framings, such as those promoted by reference to ‘libertarian paternalism’. It is argued, however, that these are inherently deficient as coherent sources of legitimacy: there may be strategic or ‘real politics’ reasons to frame justifications in this way, but the philosophical foundations of efforts to promote the public’s health require a greater—and more contestable—critical depth.
BIOGRAPHY
John Coggon is Professor of Law, and Co-Director of the Centre for Health, Law, and Society, at the University of Bristol School of Law. He has published widely on questions concerning the roles of law and governance, and the place of ethics, in public health. This includes his books What Makes Health Public? (Cambridge University Press, 2012) and, with Keith Syrett and A.M. Viens, Public Health Law: Ethics, Governance, and Regulation (Routledge, 2017). Professor Coggon is editor of the journal Health Care Analysis, and is on the editorial board of Public Health Ethics. As well as researching in public health ethics and law, he has pioneered education in the field, leading the development of University teaching on the subject, and developing and delivering training in ethics and law for the public health workforce. He also co-authored, with A.M. Viens, Public Health Ethics in Practice: An overview of public health ethics for the UK Public Health Skills and Knowledge Framework (Public Health England, 2017). In 2016, Professor Coggon was made an Honorary Member of the UK Faculty of Public Health, and is a member of the Faculty’s ethics committee.
If you would like to attend, please e-mail Jane Beinart at jane.beinart@ethox.ox.ac.uk.

T cell exhaustion is a central mechanism of immune evasion for viruses and malignancies. Despite recent scientific and medical breakthroughs demonstrating that T cell exhaustion can be overcome, important questions remain regarding the specific cellular programs governing T cell exhaustion. It is also unclear to what degree removal of persistent antigen, as the original cause for T cell exhaustion, can lead to recovery of T cell functions and memory formation. Here we utilized the unique new hepatitis C virus (HCV) therapies with direct acting antivirals (DAA) as a highly specific perturbation in a persistent viral infection in humans, as these therapies control and terminate viral replication within days of initiation of therapy. We designed a trial around DAA therapy with sampling of leukapheresis products and liver fine needle aspirates before and after treatment, enabling us to perform comprehensive immune analysis in both the blood and the liver as the site of infection. Our key findings are that virus specific CD8 T cells recover in phenotype, but little in antiviral functions post HCV cure. With regards to HCV-specific CD4 T cells, we find no significant improvement of the response in patients with treatment of chronic infection, but a rescue of these responses if treatment is initiated early after exposure. Overall our results indicate that antigen-specific T cell responses undergo partial recovery after termination of viremia, unlikely to mediate protection from re-infection. The cells might, however, be amenable to additional immunomodulatory interventions targeting remaining molecular road blocks to full functional recovery. Finally, recovery of the CD4 T cell response might be only possible during a much shorter window of opportunity after establishment of persistent viremia.

Professor Grahame Hardie

Professor D. Grahame Hardie graduated in Biochemistry from Cambridge University in 1971, and became Professor of Cellular Signalling at the University of Dundee in 1994. He is a Fellow of the Royal Society, the Royal Society of Edinburgh, and the UK Academy of Medical Sciences. He was awarded the... Read more

Professor D. Grahame Hardie graduated in Biochemistry from Cambridge University in 1971, and became Professor of Cellular Signalling at the University of Dundee in 1994. He is a Fellow of the Royal Society, the Royal Society of Edinburgh, and the UK Academy of Medical Sciences. He was awarded the Rolf Luft prize for Endocrinology and Metabolism in 2008 and the Novartis Medal of the UK Biochemical Society in 2010. He has published over 350 scientific papers and given over 200 invited lectures. His major research achievement was to define the AMP-activated protein kinase (AMPK) stem, showing it to be a key player in obesity and Type 2 diabetes that is a target for the anti-diabetic drug metformin and the anti-inflammatory drug aspirin. He also discovered that the tumour suppressor LKB1 acted upstream of AMPK, which led to the current worldwide interest in the role of AMPK in cancer and cancer treatment.

Dr Christian Grimm

My group is interested in the analysis of cation channels of the TRP (transient receptor potential) superfamily within the trafficking network of the endolysosomal system. Lysosomal dysfunction can result in endolysosomal storage disorders (LSDs) such as mucolipidoses or mucopolysaccharidoses but... Read more

My group is interested in the analysis of cation channels of the TRP (transient receptor potential) superfamily within the trafficking network of the endolysosomal system. Lysosomal dysfunction can result in endolysosomal storage disorders (LSDs) such as mucolipidoses or mucopolysaccharidoses but is also implicated in metabolic diseases, the development of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, retinal diseases and pigmentation disorders, trace metal deficiencies, infectious diseases and cancer. Highly critical for the proper function of lysosomes, endosomes, and lysosome-related organelles (LROs) is the tight regulation of various fusion and fission processes, the regulation of proton and other cation concentrations within the endolysosomal system (ES), the regulation of autophagy processes as well as endolysosomal phago- and exocytosis processes. TRPML cation channels (TRPML1, 2 and 3) and Two-pore channels (TPCs) have recently emerged as important regulators of such processes within the ES and appear to be essential for a proper communication between the various endolysosomal vesicles. We use endolysosomal patch-clamp techniques, molecular and cellular biology techniques, pharmacological approaches as well as genetic mouse models to study the physiological roles and activation mechanisms of these ion channels in-depth.

Karim Nader

Memory reconsolidation is the process in which reactivated long-term memory (LTM) becomes transiently sensitive to amnesic agents that are effective at consolidation. The phenomenon was first described more than 50 years ago but did not fit the dominant paradigm that posited that consolidation... Read more

Memory reconsolidation is the process in which reactivated long-term memory (LTM) becomes transiently sensitive to amnesic agents that are effective at consolidation. The phenomenon was first described more than 50 years ago but did not fit the dominant paradigm that posited that consolidation takes place only once per LTM item. Reconsolidation was revitalized a decade ago using auditory fear conditioning in the rat and was shown to involve neural circuitry in the basolateral amygdala. Since then, reconsolidation has been demonstrated with many species, tasks, and amnesic agents, and cellular and molecular correlates of reconsolidation have been identified. I will discuss the evidence on which reconsolidation is based, and why specific impairments in consolidation, reconsolidation and LTM maintenance always lead to memory erasure.
I will also refer to potential clinical implications of reconsolidation. These include the ability to cause the synaptic circuit manifestations of a variety of psychopathologies to become transiently un-stored. If the mechanisms mediating restabilization of these circuit changes are prevented by behavioral or pharmacological intervention, an individual’s psychopathology could be reduced within a single session. This approach has been shown to work for PTSD, drug-cue induced craving, and Phobias.

Prof Adrian Smith

We have been employing T and B cell receptor repertoire analysis tools to explore the nature of adaptive immune responses under different circumstances and in different vertebrate species. The seminar will focus on our work in mice and chickens considering how repertoire analyses can provide... Read more

We have been employing T and B cell receptor repertoire analysis tools to explore the nature of adaptive immune responses under different circumstances and in different vertebrate species. The seminar will focus on our work in mice and chickens considering how repertoire analyses can provide insight into the basic biology of T cells, infection-driven T cell tumours and microbiome-immune relationships. I will also introduce a murine system that employs restricting T cell repertoires as a tool that supports identification of protective antigens in relation to vaccine development against antigenically complex infectious agents.
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My scientific career began in Glasgow and Nottingham, considering the relationships between infection and immunity, particularly focussing on immune mechanisms in the gut. I continued this theme during a post doc in Adrian Hayday’s laboratory at Yale principally working on gut immune mechanisms and the function of TCR T cells. In 1997 I established my Enteric Immunology group at the Institute for Animal Health focussing on immunity to infection in rodent and avian systems. In 2008 I relocated my group to the Department of Zoology, Oxford where we have continued to work on aspects of innate and adaptive immunity widening our comparative approach to include an ever-widening collection of different species. Part of the group work on the evolution of pattern recognition receptors whilst others focus on adaptive immunity (including repertoire analysis) and various infection systems. Some of the group also work with ancient DNA of pathogens and their hosts.

David Watkins

We isolated human neutralizing monoclonal antibodies against the Zika virus and tested their ability to both block infection in non-human primates and to control viral replication after infection of pregnant macaques

We isolated human neutralizing monoclonal antibodies against the Zika virus and tested their ability to both block infection in non-human primates and to control viral replication after infection of pregnant macaques